Clinical Trial: Tipifarnib in Treating Patients With Myelodysplastic Syndromes

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome

Brief Summary: This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.

II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.

OUTLINE: This is a dose-escalation study.

Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria [ Time Frame: Up to 8.5 years ]
  The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.
• Response rate [ Time Frame: Up to 8.5 years ]
  Will be reported overall and by dose level.

Original Primary Outcome:

Current Secondary Outcome:

• FTase inhibition [ Time Frame: Up to 8.5 years ]
  Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
• Accumulation of unfarnesylated lamin B1 [ Time Frame: Up to 8.5 years ]
  Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
• Accumulation of RAS proteins [ Time Frame: Up to 8.5 years ]
  Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 2, 2000
Date Started: June 2002
Date Completion:
Last Updated: December 13, 2013
Last Verified: December 2013